Although it may not seem so at first glance - the immune system definitely has something to counter the attack of HI viruses. Christine Goffinet, head of the research group Innate Immunity and Viral Evasion at TWINCORE has discovered a novel antiviral mechanism with which our immune cells attack HIV immediately after infection: the protein 90K is a so-called antiviral restriction factor, which lowers the infectivity of newly formed viruses. It is expressed in macrophages, which constitute one of the cell types susceptible to HIV infection. This defense mechanism is not yet potent enough to fully combat HIV-1 infection in HIV-1 patients, but it is developable.
"Roughly a dozen antiviral genes are known that are directly upregulated following viral infections", says Christine Goffinet. Their gene products interfere with different steps of the viral replication cycle, but they cannot - as we all know - stop HIV. HIV, however, may be even more rapid and aggressive in the absence of these cellular proteins. Restriction factors are typically expressed in the presence of interferons, which constitute the body´s first innate reaction to an infection.
"We have identified 90K as a novel antiviral factor, which is upregulated together with other factors by interferons. The particularity of this protein is its antiviral working mode", the scientist says. Other factors inhibit e.g. the reverse transcription of viral genomes or the release of viruses. The new factor negatively modulates the biosynthesis and the viral incorporation of viral envelope proteins. Viruses produced in the presence of 90K are as abundant as in its absence - but the virus particles are less infectious. The spread of the virus is - at least in cell culture - impaired. This "braking action" is unfortunately not potent enough to provide the direct basis for an antiviral therapy.
The current task is to reinforce the effects of 90K against HIV and to identify a potential viral counterpart that may attenuate 90K´s effect - a so-called antagonist. Future scientific questions addressed by Christine Goffinet include: Can the protein 90K be modified in such a manner that it debilitates the virus more effectively and is, in addition, resistant to viral antagonism? "Researchers all over the world work on the characterization of these natural antiviral proteins in order to pave the way for novel therapy options", the TWINCORE researcher says. "90K may, since it displays a unique antiviral mode of action, contribute to this task."
Legend: Primary human macrophages, stimulated with interferon-alpha, following permeabilization and staining with anti-90K antibody (yellow) and DAP (cell nucleus).
Publication:
Veronika Lodermeyer, Kristina Suhr, Nicola Schrott, Christian Kolbe, Christina M. Stürzel, Daniela Krnavek, Jan Münch, Christian Dietz, Tanja Waldmann, Frank Kirchhoff, and Christine Goffinet. 90K, an interferon-stimulated gene product, reduces the infectivity of HIV-1. Retrovirology 2013, 10:111 doi:10.1186/1742-4690-10-111
Contact person:
Prof. Dr. Christine Goffinet, <link>christine.goffinet@twincore.de
Tel: +49 (0)511-220027-198